Farnesyl transferase inhibiting 6-heterocyclylmethyl quinolinone derivatives

A compound of formula (I):

• or a pharmaceutically acceptable salt or N-oxide or stereochemically isomeric form thereof, wherein
• r is 0, 1, 2, 3, 4, or 5;
• t is 0, 1, 2, or 3;
• >Y1–Y2— is a trivalent radical of formula
• >C═CR9— (y-2);
• wherein R9 is hydrogen, halo, cyano, C1-6alkyl, hydroxyC1-6alkyl, C16alkyloxyC1-6alkyl, —(CR20R21)p—C3-10cycloalkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkyloxy, halocarbonyl, hydroxycarbonyl, C1-6alkyloxycarbonyl, aryl, or a group of formula —NR22R23, —C1-6alkyl-NR22R23, —C2-6alkenyl-NR22R23, —CONR22R23, or —NR22—C1-6alkyl-NR22R23;
• p is 0 to 5;
• R20 and R21 are independently hydrogen or C1-6 alkyl and are independently defined for each iteration of p in excess of 1;
• R22 and R23 are independently hydrogen, C1-6 alkyl, or —(CR20R21)p—C3-10cycloalkyl;
• R1 is azido, hydroxy, halo, cyano, nitro, C1-6alkyl, —(CR20R21)p—C3-10cycloalkyl, cyanoC1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, hydroxycarbonylC1-6alkyloxyC1-6alkyl, R24SC1-6alkyl, trihalomethyl, arylC1-6alkyl, Het2C1-6alkyl, —C1-6alkyl-NR22R23, —C1-6alkylNR22C1-6alkyl-NR22R23, —C1-6alkylNR22COC1-6alkyl, —C1-6alkylNR22COAlkAr2, —C1-6alkylNR22COAr2, C1-6alkylsulphonylaminoC1-6alkyl, C1-6alkyloxy, hydroxyC1-6alkyloxy, C1-6alkyloxyC1-6alkyloxy, —OC1-6alkyl-NR22R23, trihalomethoxy, arylC16alkyloxy, Het2C1-6alkyloxy, C1-6alkylthio, C2-6alkenyl, cyanoC26alkenyl, —C2-6alkenyl-NR22R23, hydroxycarbonylC2-6alkenyl, C1-6alkyloxycarbonylC2-6alkenyl, C2-6alkynyl, —CHO, C1-6alkylcarbonyl, hydroxyC1-6alkylcarbonyl, hydroxycarbonyl, C1-6alkyloxycarbonyl, —CONR22R23, —CONR22—C1-6alkyl-NR22R23, —CONR22—C1-6alkyl-Het2, —CONR22—C1-6alkyl-Ar2, —CONR22—O—C1-6alkyl, —CONR22—C1-6alkenyl, —NR22R23, —OC(O)R24, —CR24═NR25, —CR24═N—OR25, —NR24C(O)NR22R23, —NR24SO2R25, —NR24C(O)R25, —S(O)0-2R24, —SO2NR24R25, —C(NR26R27)═NR28, —Sn(R24)3, —SiR24R24R25, —B(OR24)2, —P(O)OR24OR25, aryloxy, or a group of formula -Z, —CO-Z, or —CO—NRy-Z
• in which Ry is hydrogen or C1-4alkyl and Z is phenyl the phenyl ring being optionally substituted by one or two substituents each independently selected from halo, cyano, hydroxycarbonyl, aminocarbonyl, C1-6alkylthio, hydroxy, —NR22R23, C1-6alkylsulphonylamino, C1-6alkyl, haloC1-6alkyl, C1-6alkyloxy, or phenyl;
• or
• two R1 substituents adjacent to one another on the phenyl ring may form together a bivalent radical of formula
• —O—CH2—O— (a-1),
• —O—CH2—CH2—O— (a-2),
• —O—CH═CH— (a-3),
• —O—CH2—CH2— (a-4),
• —O—CH2—CH2—CH2—(a-5),
• or
• —CH═CH—CH═CH—(a-6)
• R24 and R25 are independently hydrogen, C1-6 alkyl, —(CR20R21)p-C3-10cycloalkyl, or arylC1-6alkyl;
• R26, R27, and R28 are independently hydrogen and C1-6alkyl or C(O)C1-6alkyl;
• R2 is imidazolyl;
• R3 is hydrogen, —O—R10, or —NR11R12;
• wherein
• R10 is hydrogen, C1-6alkyl, —(CR20R21)p—C3-10cycloalkyl, arylC1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkylcarbonyl, aryl, a group of formula —NR22R23R or —C1-6alkylC(O)OC1-6alkyl NR22R23, or a radical of formula -Alk-OR13, or -Alk-NR14R15;
• R11 is hydrogen, C1-6alkyl, —(CR20R21)p—C3-10cycloalkyl, C2-6alkenyl, C2-6alkynyl, aryl, or arylC1-6alkyl;
• R12 is hydrogen, hydroxy, C1-6alkyl, —(CR20R21)p—C3-10cycloalkyl, C16alkylcarbonylC1-6alkyl, arylC1-6alkyl, C2-6alkenyl, C2-6alkynyl, aryl, C1-6alkyloxy, a group of formula —NR22R23, C1-6alkylcarbonylamino, C16alkylcarbonyl, haloC1-6alkylcarbonyl, arylC1-6alkylcarbonyl, arylcarbonyl, C1-6alkyloxycarbonyl, CC16alkyloxyC1-6alkylcarbonyl, aminocarbonyl, mono- or di(C1-6alkyl)aminocarbonyl wherein the alkyl moiety may optionally be substituted by one or more substituents independently selected from aryl and C1-6alkyloxycarbonyl substituents;
• aminocarbonylcarbonyl, mono- or di(C1- di(C1-6alkyl)aminoC1-6alkylcarbonyl, or a radical of formula -Alk-OR13 or Alk-NR14R15;
• wherein Alk is C1-6alkanediyl;
• R13 is hydrogen, C1-6alkyl, —(CR20R21)p—C3-10cycloalkyl, C2-6alkenyl, C26alkynyl, C1-6alkylcarbonyl, hydroxyC1-6alkyl, aryl, or arylC1-6alkyl;
• R14 is hydrogen, C1-6alkyl, —(CR20R21)p—C3-10cycloalkyl, C2-6alkenyl, C26alkynyl, aryl, or arylC1-6alkyl;
• R15 is hydrogen, C1-6alkyl, —(CR20R21)p—C3-10cycloalkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkylcarbonyl, aryl, or arylC1-6alkyl;
• R4 is a radical of formula
• wherein
• R16 is hydrogen, halo, C1-6alkyl, —(CR20R21)p—C3-10cycloalkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, C1-6alkylS(O)0-2C1-6alkyl, C1-6alkyloxy, C1-6alkylthio, a group of formula —NR22R23, hydroxycarbonyl, C1-6alkyloxycarbonyl, or aryl;
• R17 is hydrogen, C1-6alkyl, —(CR20R21 )p—C3-10cycloalkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, aryl C1-6alkyl, trifluoromethyl, trifluoromethylC1-6alkyl, hydroxycarbonylC1-6alkyl, C1-6alkyloxycarbonylC1-6alkyl, mono- or di (C1-6alkyl)aminosulphonyl, or —C1-6alkylP(O)OR24OR25;
• R5 is cyano, hydroxy, halo, C1-6alkyl, —(CR20R21)p—C3-10cycloalkyl, C2-6alkenyl, C26alkynyl, C1-6alkyloxy, arylC1-6alkyloxy, Het2C1-6alkyloxy, hydroxycarbonyl, C1-6alkyloxycarbonyl, or a group of formula —NR22R23 or —CONR22R23;
• R6 is hydrogen;
• R7 is oxygen or sulphur;
• and Ar is phenyl.